Processing of vestibular inputs by the medullary lateral tegmental field of conscious cats: implications for generation of motion sickness.

The dorsolateral reticular formation of the caudal medulla, the lateral tegmental field (LTF), participates in generating vomiting. LTF neurons exhibited complex responses to vestibular stimulation in decerebrate cats, indicating that they received converging inputs from a variety of labyrinthine receptors. Such a convergence pattern of vestibular inputs is appropriate for a brain region that participates in generating motion sickness. Since responses of brainstem neurons to vestibular stimulation can differ between decerebrate and conscious animals, the current study examined the effects of whole-body rotations in vertical planes on the activity of LTF neurons in conscious felines. Wobble stimuli, fixed-amplitude tilts, the direction of which moves around the animal at a constant speed, were used to determine the response vector orientation, and also to ascertain whether neurons had spatial-temporal convergence (STC) behavior (which is due to the convergence of vestibular inputs with different spatial and temporal properties). The proportion of LTF neurons with STC behavior in conscious animals (25 %) was similar to that in decerebrate cats. Far fewer neurons in other regions of the feline brainstem had STC behavior, confirming findings that many LTF neurons receive converging inputs from a variety of labyrinthine receptors. However, responses to vertical plane vestibular stimulation were considerably different in decerebrate and conscious felines for LTF neurons lacking STC behavior. In decerebrate cats, most LTF neurons had graviceptive responses to rotations, similar to those of otolith organ afferents. However, in conscious animals, the response properties were similar to those of semicircular canal afferents. These differences show that higher centers of the brain that are removed during decerebration regulate the labyrinthine inputs relayed to the LTF, either by gating connections in the brainstem or by conveying vestibular inputs directly to the region.

Responses of neurons in the caudal medullary lateral tegmental field to visceral inputs and vestibular stimulation in vertical planes.

The dorsolateral reticular formation of the caudal medulla, or the lateral tegmental field (LTF), has been classified as the brain's "vomiting center", as well as an important region in regulating sympathetic outflow. We examined the responses of LTF neurons in cats to rotations of the body that activate vestibular receptors, as well as to stimulation of baroreceptors (through mechanical stretch of the carotid sinus) and gastrointestinal receptors (through the intragastric administration of the emetic compound copper sulfate). Approximately half of the LTF neurons exhibited graviceptive responses to vestibular stimulation, similar to primary afferents innervating otolith organs. The other half of the neurons had complex responses, including spatiotemporal convergence behavior, suggesting that they received convergent inputs from a variety of vestibular receptors. Neurons that received gastrointestinal and baroreceptor inputs had similar complex responses to vestibular stimulation; such responses are expected for neurons that contribute to the generation of motion sickness. LTF units with convergent baroreceptor and vestibular inputs may participate in producing the cardiovascular system components of motion sickness, such as the changes in skin blood flow that result in pallor. The administration of copper sulfate often modulated the gain of responses of LTF neurons to vestibular stimulation, particularly for units whose spontaneous firing rate was altered by infusion of drug (median of 459%). The present results raise the prospect that emetic signals from the gastrointestinal tract modify the processing of vestibular inputs by LTF neurons, thereby affecting the probability that vomiting will occur as a consequence of motion sickness.

Radial Forearm Free Tissue Transfer to Clival Defect.

Introduction Reconstruction of craniocervical junction (CCJ) defects after endoscopic endonasal skull base surgery (ESBS) remains challenging, despite advancements in vascularized intranasal and regional flaps. Microvascular free tissue transfers have revolutionized reconstruction in open skull base surgery but have been utilized rarely in ESBS. We describe the use of a radial forearm free flap (RFFF) for reconstruction of a recalcitrant CCJ defect after resection of a clival chordoma. Case Report A 54-year-old female who underwent ESBS for a clival chordoma complicated by a C1-C2 epidural abscess after proton beam therapy presented with pneumocephalus 4 years after her resection ( Fig. 1 ). At the CCJ, she developed a 1-cm skull-base defect. An occult cerebrospinal fluid (CSF) leak persisted despite an extracranial pericranial flap and a lateral nasal wall flap. Her definite reconstruction was a RFFF inset through a transmaxillary approach. Using a maxillary vestibular incision, anterior, lateral, and medial maxillotomies allowed the introduction of the flap into the nasal cavity and the passage of the RFFF pedicle across the posterior maxillary wall, into the premassateric space and to the facial vessels at the mandible. An endonasal inset supplemented with transoral suturing of the distal end of the flap to the posterior oropharynx halted further CSF egress. Vascularization of the flap was confirmed with intraoperative indocyanine green angiography and postoperative computed tomography (CT) angiography and magnetic resonance imaging (MRI). Conclusion A RFFF inset through a transmaxillary approach to the facial vessels has an adequate reconstructive surface and pedicle to cover the central and posterior fossa skull base after ESBS ( Fig. 2 ). The link to the video can be found at: https://youtu.be/rQ5vJKyD5qg .

Biological mechanisms of immune escape and implications for immunotherapy in head and neck squamous cell carcinoma.

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors. Preclinical and early phase trials have shown unprecedented efficacy with minimal adverse effects. This article will review biological mechanisms of immune escape and implications for immunotherapy in HNSCC.

Malignant Otitis Externa: Evolving Pathogens and Implications for Diagnosis and Treatment.

OBJECTIVE: Malignant otitis externa (MOE) is an invasive infection of the temporal bone that is classically caused by Pseudomonas aeruginosa. Increasingly, however, nonpseudomonal cases are being reported. The goal of this study was to evaluate and compare the clinical presentation and outcomes of cases of MOE caused by Pseudomonas versus non-Pseudomonas organisms. STUDY DESIGN: Retrospective case series with chart review. SETTING: Tertiary care institution. SUBJECTS AND METHODS: Adult patients with diagnoses of MOE between 1995 and 2012 were identified. Charts were reviewed for history, clinical presentation, laboratory data, treatment, and outcomes. RESULTS: Twenty patients diagnosed with and treated for MOE at the University of Pittsburgh Medical Center between 1995 and 2012 were identified. Nine patients (45%) had cultures that grew P aeruginosa. Three patients (15%) had cultures that grew methicillin-resistant Staphylococcus aureus (MRSA). Signs and symptoms at presentation were similar across groups. However, all of the patients with Pseudomonas had diabetes, compared with 33% of MRSA-infected patients (P = .046) and 55% of all non-Pseudomonas-infected patients (P = .04). Patients infected with MRSA were treated for an average total of 4.7 more weeks of antibiotic therapy than Pseudomonas-infected patients (P = .10). Overall, patients with non-Pseudomonas infections were treated for a total of 2.4 more weeks than Pseudomonas-infected patients (P = .25). CONCLUSIONS: A high index of suspicion for nonpseudomonal organisms should be maintained in patients with signs and symptoms of MOE, especially in those without diabetes. MRSA is an increasingly implicated organism in MOE.

Responses of vestibular nucleus neurons to inputs from the hindlimb are enhanced following a bilateral labyrinthectomy.

Vestibular nucleus neurons have been shown to respond to stimulation of afferents innervating the limbs. However, a limitation in the potential translation of these findings is that they were obtained from decerebrate or anesthetized animals. The goal of the present study was to determine whether stimulation of hindlimb nerves similarly affects vestibular nucleus neuronal activity in conscious cats, and whether the responsiveness of neurons to the stimuli is altered following a bilateral labyrinthectomy. In labyrinth-intact animals, the firing rate of 24/59 (41%) of the neurons in the caudal vestibular nucleus complex was affected by hindlimb nerve stimulation. Most responses were excitatory; the median response latency was 20 ms, but some units had response latencies as short as 10 ms. In the first week after a bilateral labyrinthectomy, the proportion of vestibular nucleus neurons that responded to hindlimb nerve stimulation increased slightly (to 24/55 or 44% of units). However, during the subsequent postlabyrinthectomy survival period, the proportion of vestibular nucleus neurons with hindlimb inputs increased significantly (to 30/49 or 61% of units). Stimuli to hindlimb nerves needed to elicit neuronal responses was consistently over three times the threshold for eliciting an afferent volley. These data show that inputs from hindlimb afferents smaller than those innervating muscle spindles and Golgi tendon organs affect the processing of information in the vestibular nuclei, and that these inputs are enhanced following a bilateral labyrinthectomy. These findings have implications for the development of a limb neuroprosthetics device for the management of bilateral vestibular loss.